UniProt Accession

 UHRF1_MOUSE; Q8VDF2; Q3U9D7; Q3U9P2; Q3UI74; Q3UIE6; Q3ULF2; Q3ULQ0; Q8C6F1; Q8VIA1; Q9Z1H6 

Genbank Protein ID

 D87908; AF274046; AK075819; AK143688; AK145376; AK145543; AK146951; AK147046; AK150489; AK151701; AK151837; AK152930; AK153083; AC026385; BC022167; AB066246 

Genbank Nucleotide ID

 BAA74579.1; AAK55743.1; BAC35985.1; BAE25499.1; BAE26398.1; BAE26496.1; BAE27560.1; BAE27632.1; BAE29605.1; BAE30624.1; BAE30730.1; BAE31605.1; BAE31708.1; AAH22167.1; BAB79496.1 

Protein Name

 E3 ubiquitin-protein ligase UHRF1 

Protein Synonyms/Alias

 Nuclear protein 95; Nuclear zinc finger protein Np95; Ubiquitin-like PHD and RING finger domain-containing protein 1; mUhrf1; Ubiquitin-like-containing PHD and RING finger domains protein 1 

Gene Name

 Uhrf1 

Gene Synonyms/Alias

 Np95 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
24	NSLSRLTKVQELRKK	ubiquitination	[1]
157	AQVVQVQKRALSEDE	ubiquitination	[1]
196	EHGVDIVKAKNVRAR	ubiquitination	[1]
381	EVVQAGEKLKESKKK	acetylation	[2]
505	AGQSSDQKLTNNNRA	ubiquitination	[1]
664	PRASKKSKLEPYTLS	acetylation	[2]

Reference

 [1] BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.
 Mathew R, Seiler MP, Scanlon ST, Mao AP, Constantinides MG, Bertozzi-Villa C, Singer JD, Bendelac A.
 Nature. 2012 Nov 22;491(7425):618-21. [PMID: 23086144]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337] 

Functional Description

 Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD- type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair. 

Sequence Annotation

 DOMAIN 1 78 Ubiquitin-like.
 DOMAIN 424 586 YDG.
 ZN_FING 304 371 PHD-type.
 ZN_FING 713 752 RING-type.
 REGION 129 205 Tudor-like 1.
 REGION 212 280 Tudor-like 2.
 REGION 293 306 Linker (By similarity).
 REGION 338 342 Histone H3R2me0 binding (By similarity).
 REGION 358 360 Histone H3R2me0 binding (By similarity).
 REGION 450 451 Required to promote base flipping.
 REGION 468 469 Methylcytosine binding (By similarity).
 REGION 471 474 Required for formation of a 5-
 REGION 483 486 Required for formation of a 5-
 BINDING 321 321 Histone H3K4me0 (By similarity).
 BINDING 332 332 Histone H3R2me0 (By similarity).
 BINDING 335 335 Histone H3R2me0 (By similarity).
 BINDING 474 474 Methylcytosine (By similarity).
 MOD_RES 76 76 Phosphoserine (By similarity).
 MOD_RES 91 91 Phosphoserine (By similarity).
 MOD_RES 303 303 Phosphoserine; by PKA (By similarity).
 MOD_RES 404 404 N6-acetyllysine (By similarity).
 MOD_RES 550 550 N6-acetyllysine (By similarity).
 MOD_RES 639 639 Phosphoserine; by CDK1 (By similarity).
 MOD_RES 649 649 Phosphoserine (By similarity).
 CROSSLNK 390 390 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Cell cycle; Chromatin regulator; Complete proteome; DNA damage; DNA repair; DNA-binding; Isopeptide bond; Ligase; Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 782 AA 

Protein Sequence

Gene Ontology

 GO:0000791; C:euchromatin; ISS:UniProtKB.
 GO:0000792; C:heterochromatin; IDA:UniProtKB.
 GO:0000790; C:nuclear chromatin; IDA:UniProtKB.
 GO:0016363; C:nuclear matrix; IDA:BHF-UCL.
 GO:0005657; C:replication fork; IDA:UniProtKB.
 GO:0044729; F:hemi-methylated DNA-binding; IDA:UniProtKB.
 GO:0035064; F:methylated histone residue binding; IDA:UniProtKB.
 GO:0031493; F:nucleosomal histone binding; IDA:BHF-UCL.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:BHF-UCL.
 GO:0008270; F:zinc ion binding; ISS:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0008283; P:cell proliferation; TAS:MGI.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0010390; P:histone monoubiquitination; IDA:BHF-UCL.
 GO:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR021991; DUF3590.
 IPR014722; Rib_L2_dom2.
 IPR003105; SRA_YDG.
 IPR000626; Ubiquitin.
 IPR019955; Ubiquitin_supergroup.
 IPR011011; Znf_FYVE_PHD.
 IPR001965; Znf_PHD.
 IPR019787; Znf_PHD-finger.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 

Pfam

 PF12148; DUF3590
 PF00628; PHD
 PF00240; ubiquitin
 PF02182; YDG_SRA 

SMART

 SM00249; PHD
 SM00184; RING
 SM00466; SRA
 SM00213; UBQ 

PROSITE

 PS00299; UBIQUITIN_1
 PS50053; UBIQUITIN_2
 PS51015; YDG
 PS01359; ZF_PHD_1
 PS50016; ZF_PHD_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 

PRINTS